Method and composition for the treatment of cancer by the enzymatic conversion of soluble radioactive toxic agents into radioactive toxic precipitates in the cancer

摘要

A method for the treatment of cancer is disclosed which is capable of directing supra-lethal doses of radiation, called Hot-Spots, virtually exclusively to the cancer. The present invention involves a multi-step therapy process and includes a class of novel chemical agents. In accordance with the present invention, it was discovered that soluble precipitable materials can be made to accumulate as non-digestible precipitates in targeted cells as a result of enzyme action within the targeted cells. Accumulation is achieved by administering to the living host a soluble binary reagent made by attaching a targeting agent to a novel chemical agent which is a soluble precipitable material. The binary reagent binds to antigenic receptors on targeted cells which endocytose the binary reagent and transport it into the lysosomes where enzymes detach the soluble precipitable material from the targeting agent, causing it to precipitate, accumulate, and be retained in the cells. Increasing amounts of precipitate can be made to accumulate in cells by continuing the administration of the binary reagent. The accumulated precipitate is relocated to the extra-cellular fluid by selectively killing a fraction of cancer cells. Now relocated in the extra-cellular fluid of the cancer, the precipitate is used as a “platform” from which to generate Hot-Spots. A bispecific reagent with a non-mammalian enzyme moiety is made to bind to the precipitate. A soluble radioactive material is administered which is converted by the enzyme moiety of the bound bispecific reagent into a new form which is retained adjacent to the precipitate for an extended period of time, thereby generating Hot-Spots which non-selectively kill all cells adjacent to the precipitate in the extra-cellular fluid of the cancer.